Gaetti then spent the next three years in the Twins' minor league system, playing for the rookie level Elizabethton Twins in the Appalachian League in 1979, the A-level Wisconsin Rapids Twins in the Midwest League in 1980, and the AA-level Orlando Twins in the Southern League in 1981. Gaetti then made his major league debut in nine September games which included hitting a home run in his first major league at bat. In 1982, Gaetti would become a permanent fixture at third base for the Twins and would man the hot corner in Minnesota for the next nine seasons.

Gaetti with St. Louis

In 1986, Gaetti batted .287 with 34 home runs and 108 runs batted in. Gaetti won four consecutive Gold Glove Awards for fielding excellence from 1986 through 1989. Gaetti helped propel the Twins to the 1987 post-season and their first World Series championship, hitting .257 with 31 home runs and 109 RBI. He also hit himself into the record books, with home runs in his first two career postseason plate appearances[3] in the American League Championship Series to help the Twins upset the Detroit Tigers.

Gaetti was selected as an All-Star in 1988 and 1989. Playing against the Boston Red Sox on July 17, 1990, Gaetti helped the Twins make history as the team became the only team in baseball history to turn two triple plays in the same game. Despite their defensive heroics, the Twins lost the game 1–0.[4][5]

His production at the plate would decline[6] and after hitting only .229 in 1990, Gaetti left the Twins for the Angels as a free agent. His production continued to drop off with the Angels and midway through the third year of his four-year contract, he was released, in June 1993. He was almost immediately signed by the Royals, who had lost their projected regular third baseman, Keith Miller, to injury and had been playing rookie Phil Hiatt at third. Gaetti hit 26 home runs for the Royals in 665 at-bats between 1993 and 1994, splitting time at third with Miller, David Howard, and Terry Shumpert. In 1995, Gaetti played in 137 games and at the age of 36, he hit .261 with 35 home runs and 96 RBI, winning his only Silver Slugger,[6] setting a career high in home runs and missing the Royals' team record for most home runs in a season by one.

Following the 1995 season, Gaetti signed as a free agent with the Cardinals, where he enjoyed two more productive seasons before being released again in August 1998 after the Cardinals' acquisition of Fernando Tatís. Gaetti immediately signed with the Cubs, where he hit .320/8/27 as the Cubs won the National League wild card. The following season, Gaetti played only semi-regularly and was released at the end of the season after hitting .204 with 9 home runs. He wound up his career the following season in Boston, appearing in five games in April 2000 at the age of 41.

Bill James noted Gaetti's baseball-related aging process as being unusual for two reasons. Unlike most other league veterans, his walk rate never improved and his rate of productivity decline was "exceptionally" slow.[7] Gaetti retired as the all-time home run king of players who homered in their first Major League at bat. Gaetti was used as an emergency relief pitcher by both the Cardinals and the Cubs, retiring with an ERA of 7.71 and one strikeout in three appearances.

Gaetti was inducted into the NWMSU athletic hall of fame, the "M-Club", in October 2003. He coached in the Houston Astros minor league system as a hitting coach with the AAA New Orleans Zephyrs from 2002 to 2004.[8] Gaetti was promoted to hitting coach for the Astros on July 14, 2004 when the team dismissed manager Jimy Williams, hitting coach Harry Spilman, and pitching coach Burt Hooton. Gaetti remained in this position until July 12, 2006, when he was fired by the Astros. Following the season, he was hired as the hitting coach for Tampa Bay's AAA affiliate, the Durham Bulls - a position he would hold through the 2008 season.[9] After working at Baseball USA in Houston, Texas in 2011,[10] Gaetti was named the first manager of the Sugar Land Skeeters.[1] The independent team began plan in 2012.

On August 19, 2007, Gaetti's 49th birthday, the Minnesota Twins inducted him into the team's Hall of Fame, while the club simultaneously released a commemorative bobblehead in his honor. On October 2, 2008, former Durham Bull, rookie Evan Longoria, joined Gaetti in the record books by hitting home runs in his first two post-season at-bats.